Note: The information on the coronavirus outbreak is continually evolving. The content within this activity serves as a historical reference to the information that was available at the time of this publication. We continue to add to the collection of activities on this subject as new information becomes available. It is the policy of Medscape Education to avoid the mention of brand names or specific manufacturers in accredited educational activities. However, manufacturer names related to the approved COVID-19 vaccines are provided in this activity in an effort to promote clarity. The use of manufacturer names should not be viewed as an endorsement by Medscape of any specific product or manufacturer.

Clinical Context

SARS-CoV-2 has significant morbidity and mortality in patients with immune-mediated inflammatory diseases (IMIDs). Immune dysfunction and treatment with immune modulatory drugs affect responses to infection and vaccination, with variable effectiveness, longevity, and protection against poor outcomes.

Most people with IMIDs can mount humoral immune responses to SARS-CoV-2 infection and vaccination, but these appear blunted, with lower prevalence of anti--SARS-CoV-2 antibody positivity from infection than in the general population. As anti-SARS-CoV-2 IgG titers correlate with COVID-19 risk and vaccine effectiveness, this may warn of waning immunity.

Study Synopsis and Perspective

A new study in The Lancet Rheumatology ^[1] examined the strength and duration of SARS-CoV-2 vaccine-induced immunoglobulin-G antibody responses over time for patients with a variety of autoimmune diseases compared with healthy control participants.

The presence of humoral antibodies to SARS-CoV-2 has been shown to correlate with protection against COVID-19, but for patients with IMIDs, host response to COVID-19 or to vaccination is affected by the immune dysfunction imposed by the IMIDs and by the use of immune-modulating drugs to treat it.

This new study found a weaker -- as shown previously^[2] -- and less sustained immune response to SARS-CoV-2 vaccines in patients with a variety of IMIDs, including rheumatoid arthritis; spondyloarthritis; psoriasis; inflammatory bowel diseases; and other systemic autoimmune diseases, such as lupus. It also pointed toward the possibility of adjusting treatment and vaccination schedules and strategies for these patients based on their antibody levels, among other factors, to preserve best protection against severe COVID-19.

"It is important to assess immune response in these patients to see if they still have protection against severe COVID infection," said lead author David Simon, MD, senior clinical scientist in clinical immunology and rheumatology at University Hospital Erlangen, Germany. "We know that antibody response is an immune correlate. Therefore, it is important to see how large and durable the immune response is to the coronavirus vaccine in these IMID patients, and whether specific drugs or therapies have negative effects on their immune response."

For this large prospective cohort study,^[1] researchers registered 5076 coronavirus-vaccinated individuals. They analyzed serum samples obtained between December 15, 2020 and December 1, 2021 from 2535 patients diagnosed with IMIDs and participating in a prospective coronavirus study program at the Deutsches Zentrum Immuntherapie in Erlangen, Germany. The patients with IMIDs had a mean age of 55 ± 15.2 years, and 58.9% were women.

A healthy control group of 1198 individuals without IMIDs who had a mean age of 40.7 ± 13.5 years, including 53.8% men, was also recruited for the analysis. All approved coronavirus vaccines were included, following standard vaccination schedules. Antibody response was measured over time by an enzyme-linked immunosorbent assay from 8 weeks after first vaccination to week 40.

Among the findings, the healthy control participants had higher postvaccine antibody levels than did patients with IMIDs, but the majority of vaccinated patients with IMIDs were able to build up a humoral immune response to SARS-CoV-2. Patients who were taking B-cell inhibitors and T-cell inhibitors for IMIDs had significantly poorer antibody response.

Greater age and the use of combination therapies for IMIDs compared with monotherapy further reduced immune response to the vaccine. In terms of vaccination modality, messenger RNA (mRNA)-based vaccines induced higher antibody levels than did vector-based vaccines. The researchers noted that patients with IMIDs who were given a third vaccine dose could actually catch up well with the antibody responses observed in healthy control participants.

"We looked at whether different IMIDs had a different humoral response, and we also assessed if there are effects from different therapeutic strategies," Simon explained. "It doesn't matter so much what kind of IMID patients have; much more important is the specific drug treatment and its impact on their antibody response."

Some participants were advised to briefly stop taking some immunosuppressive treatments before or after vaccination.

One of Simon's coauthors, statistician and rheumatologist Koray Tascilar, MD, added, "This research is important because we looked not only at who responded less, which has been previously established, but who are at greater risk of losing their immune response, and how quickly."

Need to Take Care

It is important to be able to tell patients which drugs are safe and will not have a negative impact on their immune response to vaccinations, Tascilar said, "[b]ut it would be too strong to say we're ready to choose therapies based on their potential impact on protection against COVID. Yes, there is a risk from catching COVID, but we need to balance that risk with the risk of not giving patients the medications that are necessary to treat their rheumatologic condition."

"This study, along other recent studies, has found that antibody levels in patients with immune-mediated diseases wane more rapidly than in healthy controls, and this is especially true of those on medications that interfere with the B and T cells and anti-cytokine therapies," Rebecca Haberman, MD, assistant professor, division of rheumatology, New York University Langone Health, New York, New York, in an email to Medscape Medical News.

"While there is no known antibody level that specifically correlates with clinical protection, and each patient needs to be thought of individually, these findings support the use of supplemental booster dosing in patients with immune-mediated inflammatory diseases," Haberman said, adding that her own research in this area^[3] has shown similar results.

"As a rheumatologist, I would be more likely to encourage my patients -- especially those on immunomodulatory medications -- to get boosted," stated Haberman.

Tascilar said their study^[1] does not directly answer the question of whether an earlier booster shot would be an effective strategy for patients with IMID.

She advised that the decision of revaccination or not, and when, is based on a number of factors, not only on the level of antibodies.

The study was supported by the Deutsche Forschungsgemeinschaft. Simon and Tascilar declared no relevant financial relationships.

Clinical Implications

• People with IMIDs have lower, less durable SARS-CoV-2 vaccination response and greater risk of losing humoral immune protection.
• The findings could help guide disease control and prevention policy makers and support reconsideration of current vaccination recommendations.
• Implications for the Healthcare Team: Adjusted vaccination schedules with earlier boosters and/or more frequent redoses could better protect people with IMIDs. Members of the healthcare team should also be prepared to offer education on patient specific treatments and impact on COVID-19 protection, based on current data.

Earn Credit